U.S. patent number 6,066,597 [Application Number 09/361,906] was granted by the patent office on 2000-05-23 for herbicidal 2-(hetero)aryloxy-6-arylpyridines and 2-aryl-4-(hetero)aryloxy-6-arylpyridines and 2-aryl-4-(hetero)aryloxypyrimidines.
This patent grant is currently assigned to American Cyanamid Company. Invention is credited to Helmut Siegfried Baltruschat, Thekla Haselwander, Axel Kleemann.
United States Patent |
6,066,597 |
Kleemann , et al. |
May 23, 2000 |
Herbicidal 2-(hetero)aryloxy-6-arylpyridines and
2-aryl-4-(hetero)aryloxy-6-arylpyridines and
2-aryl-4-(hetero)aryloxypyrimidines
Abstract
New herbicidal pyridine and pyrimidine derivatives of general
formula (I), ##STR1## wherein Z represents a nitrogen atom or a
C--H group; A represents an optionally substituted aryl group or an
optionally substituted 5- or 6-membered nitrogen-containing
heteroaromatic group; n represents an integer from 0 to 2 and
R.sup.1 or each R.sup.1 independently represents a hydrogen atom or
an optionally substituted alkyl, alkoxy, alkylthio or dialkylamino
group; m represents an integer from 0 to 5 and R.sup.2 or each
R.sup.2 independently represents a hydrogen or a halogen atom or an
optionally substituted alkyl, haloalkyl, haloalkoxy, alkoxy,
alkylthio group or a nitro, cyano or a halosulphonyl group; and X
represents an oxygen or sulphur atom.
Inventors: |
Kleemann; Axel (Konigstein,
DE), Baltruschat; Helmut Siegfried (Schweppenhausen,
DE), Haselwander; Thekla (Weil am Rhein,
DE) |
Assignee: |
American Cyanamid Company
(Madison, NJ)
|
Family
ID: |
27037318 |
Appl.
No.: |
09/361,906 |
Filed: |
July 27, 1999 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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115275 |
Jul 14, 1998 |
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761479 |
Dec 6, 1996 |
5824624 |
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454044 |
May 30, 1995 |
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Current U.S.
Class: |
504/251; 504/230;
504/238; 504/242; 504/253; 544/219; 544/239; 544/333; 544/405;
546/256; 546/276.1 |
Current CPC
Class: |
A01N
43/40 (20130101); A01N 43/54 (20130101); A01N
43/56 (20130101); C07D 213/61 (20130101); C07D
213/64 (20130101); C07D 213/643 (20130101); C07D
239/30 (20130101); C07D 239/36 (20130101); C07D
401/12 (20130101) |
Current International
Class: |
A01N
43/40 (20060101); A01N 43/54 (20060101); A01N
43/34 (20060101); A01N 43/48 (20060101); A01N
43/56 (20060101); C07D 213/00 (20060101); C07D
239/36 (20060101); C07D 239/00 (20060101); C07D
213/61 (20060101); C07D 213/643 (20060101); C07D
239/30 (20060101); C07D 213/64 (20060101); C07D
401/00 (20060101); C07D 401/12 (20060101); C07D
401/12 (); A01N 043/40 () |
Field of
Search: |
;546/276.1,261
;504/253,251,238,242,230 ;544/219,333,405,239 |
References Cited
[Referenced By]
U.S. Patent Documents
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|
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3576616 |
April 1971 |
Nowotny et al. |
3637720 |
January 1972 |
Nishiyama et al. |
4405743 |
September 1983 |
Nishimura et al. |
4493726 |
January 1985 |
Burdeska et al. |
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Foreign Patent Documents
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0263958-A1 |
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Apr 1988 |
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EP |
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0354766-A2 |
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Feb 1990 |
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EP |
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0425247-A1 |
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May 1991 |
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EP |
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0572093-A1 |
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Dec 1993 |
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EP |
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4029654 |
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Sep 1990 |
|
DE |
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2131480A |
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Feb 1989 |
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JP |
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Other References
Inouye et al., Journal of Fluorine Chemistry, 27, pp. 231-236
(1985)..
|
Primary Examiner: Fan; Jane
Attorney, Agent or Firm: Babcock; Timothy J.
Parent Case Text
This is a divisional of copending application Ser. No. 09/115,275
filed on Jul. 14, 1998 the entire disclosure of which is hereby
incorporated by reference which is a division of Ser. No.
08/761,479, filed Dec. 6, 1996, now U.S. Pat. No. 5,824,624 which
is a continuation of Ser. No. 08/454,044 filed May. 30, 1995, now
abandoned.
Claims
We claim:
1. A compound of the general formula I ##STR23## wherein Z
represents a C--H group;
A represents an optionally substituted 5- or 6-membered
nitrogen-containing heteroaromatic group selected from pyrazolyl,
imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl
and triazinyl, wherein the heteroaromatic groups are optionally
substituted by one or more of the same or different substitutents
selected from halogen, nitro, cyano, amino, hydroxyl, C1-4-alkyl,
C1-4-alkoxy, C1-4-haloalkyl, C1-4-haloalkoxy and halosulphonyl
groups;
n represents an integer from 0 to 2 and R.sup.1 or each R.sup.1
independently represents a hydrogen atom or an optionally
substituted alkyl, alkoxy, alkylthio or dialkylamino group;
m represents an integer from 0 to 5 and R.sup.2 or each R.sup.2
independently represents a hydrogen or a halogen atom or an
optionally substituted alkyl, haloalkyl, haloalkoxy, alkoxy,
alkylthio group or a nitro, cyano or a halosulphanyl group; and
X represents an oxygen or sulphur atom;
with the proviso that when
Z represents a C--H group, A represents a
1-methyl-3-trifluoromethyl-pyrazol-5-yl group,
n is 0 and X represents an oxygen atom, then
m must be other than 0, and when m is 1 then
R.sup.2 cannot be a 3-trifluoromethyl substituent and when m is
2
then R.sup.2 cannot be a 2,4 dichloro substituent or a 2,4 dimethyl
substitutent.
2. A compound as claimed in claim 1 wherein
A represents a pyridyl or pyrazolyl group being substituted by one
or more of the same or different substituents selected from halogen
atoms, alkyl groups, alkoxy groups, haloalkyl groups, haloalkoxy
groups and pentahalosulphonyl groups.
3. A compound as claimed in claim 2 wherein
A has a substituent in the meta-position relative to the point of
attachment.
4. A compound as claimed in claim 3 wherein
A is meta-substituted by a chlorine atom or a trifluoromethyl
group.
5. A compound as claimed in claim 1 wherein
X is oxygen.
6. A compound as claimed in claim 1 selected from the group
consisting of:
2-(1'-methyl-3'-trifluoromethylpyrazol-5'-yloxy)-6-(4"-trifluoromethylpheny
l)pyridine,
2-(2'-chloropyrid-4'-yloxy)-(4"-trifluoromethylphenyl)pyridine,
2-(2'-chloropyrid-4'-yloxy)-6-(3"-trifluoromethylphenyl)pyridine,
4-methyl-6-(4"-trifluoromethoxyphenyl)-2-(1'-methyl-3'-trifluoromethylpyraz
ol-5'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethoxyphenyl)-2-(2'-chloropyrid-4'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethylphenyl)-2-(1'-methyl-3'-trifluoromethylpyrazo
l-5'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethylphenyl)-2-(2'-chloropyrid-4'-yloxy)pyridine,
and
6-(4"-fluorophenyl)-2-(1'-methyl-3'-trifluoromethylpyrazol-5'-yloxy)pyridin
e.
7. A herbicidal composition which comprises at least one compound
of formula I as defined in claim 1 and a carrier and/or a
surface-active agent.
8. A method of combating undesired plant growth at a locus, which
comprises treating the locus with at least one compound of formula
I as defined in claim 1.
Description
The present invention relates to certain 2,6-disubstituted
pyridines and 2,4-disubstituted pyrimidines, their preparation and
use as herbicides.
Pyridines, pyrimidines and their derivatives have many uses in the
pharmaceutical area as well as in agriculture (herbicides,
fungicides, acaricides, anthelmintics, bird repellents), reagents,
intermediates and chemicals for the polymer and textile
industry.
2-Arylpyrimidines and 2-pyrimidinyl-6-arylpyridines for example
have been described as fungicides (DE 40 29 654 and JO 2131-480,
respectively). EP 263,958 is concerned with herbicidal
2,6-diphenylpyridines, and structurally related
2,4-diphenylpyrimidines have been disclosed in EP 354,766 and
425,247, respectively, which are also said to be herbicides.
Another example are 2,6-diphenoxypyridines, which have been
published in EP 572,093 as herbicides.
4-Phenoxy-2-pyrazol-1-yl-pyrimidines are disclosed in DE 29 35 578
to have fungicidal activity. Huelsen (Diplomarbeit, Konstanz 1993)
describes four distinct
2-(1-methyl-3-trifluoromethyl-pyrazol-5-ylyoxy)-6-phenyl pyridines,
however, no biological activity is disclosed.
Surprisingly, it has now been found that good herbicidal activity
is present in related, novel pyridine and pyrimidine derivatives
having both an aryl group and an aryloxy or a heteroaryloxy group.
These compounds unexpectedly show excellent activity and good crop
selectivity in pre- and post-emergence applications on both
broadleaf and grassy weed species.
Accordingly, the present invention provides 2,6-substituted
pyridines and 2,4-substituted pyrimidines of the general formula I
##STR2## wherein Z represents a nitrogen atom or a C--H group; A
represents an optionally substituted aryl group or an optionally
substituted 5- or 6-membered nitrogen-containing heteroaromatic
group; n represents an integer from 0 to 2 and R.sup.1 or each
R.sup.1 independently represents a hydrogen atom or an optionally
substituted alkyl, alkoxy, alkylthio or dialkylamino group; m
represents an integer from 0 to 5 and R.sup.2 or each R.sup.2
independently represents a hydrogen or a halogen atom or an
optionally substituted alkyl, haloalkyl, haloalkoxy, alkoxy,
alkylthio group or a nitro, cyano or a halosulphonyl group; and X
represents an oxygen or sulphur atom; with the proviso that when Z
is C--H, A is 1-methyl-3 trifluoromethyl-pyrazol-5-yl, n is 0 and X
is oxygen, then m must be other than 0 and when m is 1 then R.sup.2
cannot be a 3-trifluoromethyl substituent and when m is 2, then
R.sup.2 cannot be a 2,4-dichloro substituent or a 2,4 dimethyl
substituent.
An aryl group as substituent or part of other substituents is
suitably an optionally substituted phenyl or naphthyl group. A 5-
or 6-membered heteroaryl group comprises optionally substituted 5-
or 6 membered heterocycles containing one or more nitrogen and/or
oxygen and/or sulfur atoms, 1 to 3 nitrogen atoms being preferred.
Example of such groups are pyrazolyl, imidazolyl, triazolyl,
tetrazolyl, pyridyl, pyrazinyl, pyridazinyl and triazinyl
groups.
Generally, when any of the above mentioned moieties comprises an
alkyl group, this alkyl group, unless otherwise specified, may be
linear or a branched and may suitably contain 1 to 12, preferably 1
to 4, carbon atoms. Examples of such groups are methyl, ethyl,
propyl, isopropyl, isopropyl, butyl, isobutyl and tertiary-butyl
groups. An alkyl portion of a haloalkyl, haloalkoxy, alkylthio or
alkoxy group suitably has from 1 to 4 carbon atoms, preferably 1 or
2 carbon atoms.
Halogen represents a fluorine, chlorine, bromine or iodine atom.
Haloalkyl and haloalkoxy are preferably mono-, di- or
trifluoroalkyl and -alkoxy,
especially trifluoromethyl and trifluoromethoxy.
When any groups are designated as being optionally substituted, the
substituent groups which are optionally present may be any of those
customarily employed in the modification and/or development of
pesticidal compounds and are especially substituents that maintain
or enhance the herbicidal activity associated with the compounds of
the present invention, or influence persistence of action, soil or
plant penetration, or any other desirable property of such
herbicidal compounds. There may be one or more of the same or
different substituents present in each part of the molecules. In
relation to moieties defined above as comprising an optionally
substituted alkyl group, including alkyl parts of haloalkyl,
alkoxy, alkylthio haloalkoxy and dialkylamino groups, specific
examples of such substituents include phenyl, nitro, cyano,
hydroxyl, C.sub.1-4 -alkoxy, C.sub.1-4 -haloalkoxy and C.sub.1-4
-alkoxycarbonyl groups.
In relation to moieties defined above as comprising an optionally
substituted aryl or heteroaryl group, optional substituents include
halogen, especially fluorine, chlorine and bromine and nitro,
cyano, amino, hydroxyl, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy,
C.sub.1-4 -haloalkyl, C.sub.1-4 -haloalkoxy and halosulphonyl
groups. 1 to 5 substituents may suitably be employed, 1 to 2
substituents being preferred.
The compounds according to general formula I are oils, gums, or,
predominantly, crystalline solid materials. They can be used in
agriculture or related fields for the control of undesired plants
such as Alopecurus myosuroides, Echinochloa crus-galli, Setaria
viridis, Galium aparine, Stellaria media, Veronica persica, Lamium
purpureum, Viola arvensis, Abutilon theophrasti, lpomoea purpurea
and Amaranthus retroflexus by pre- and post-emergence application.
The compounds of general formula I according to the invention
possess a high herbicidal activity within a wide concentration
range and may be used in agriculture without any difficulties.
Preferred compounds are those wherein A represents a phenyl,
pyridyl, or pyrazolyl group, being substituted by one or more
identical or different substituents selected from halogen atoms,
alkyl, alkoxy, haloalkyl, haloalkoxy and pentahalosulphonyl
groups.
Especially preferred are compounds bearing a substituent in group A
in meta-position relative to the point of attachment of this
group.
Good results in terms of control of undesired plant growth are
obtained when A is meta-substituted by a chlorine atom or a
trifluoromethyl group, especially A being a 2-chloropyrid-4-yl,
1-methyl-3-trifluoromethylpyrazol-5-yl or 3-trifluoromethylphenyl
group.
Particularly good results in control of weeds are achieved with
compounds wherein X represents an oxygen atom.
Especially good results are obtained with compounds wherein Z
represents a nitrogen atom.
Among the compounds exemplified by the invention are the following
compounds:
2-(1'-methyl-3'-trifluoromethylpyrazol-5'-yloxy)-6-(4"-trifluoromethylpheny
l)pyridine,
2-(2',4'-difluorophenyl)-6-methyl-4-(1"-methyl-3"-trifluoromethylpyrazol-5"
-yloxy)pyrimidine,
2-(2',4'-difluorophenyl)-6-methyl-4-(3"-trifluoromethylphenoxy)pyrimidine,
2-(2'-chloropyrid-4'-yloxy)-(4"-trifluoromethylphenyl)pyridine,
2-(2'-chloropyrid-4'-yloxy)-6-(3"-trifluoromethylphenyl)pyridine,
2-(3'-chlorophenyl)-5-methyl-4-(1"-methyl-3"-trifluoromethylpyrazol-5"-ylox
y)pyrimidine,
2-(3'-chlorophenyl)-5-methyl-4-(3"-trifluoromethylphenoxy)pyrimidine,
2-(4'-fluorophenyl)-6-methyl-4-(3"-trifluoromethylphenoxy)
pyrimidine,
2-(4'-fluorophenyl)-4-(1"-methyl-3"-trifluoromethylpyrazol-5"-yloxy)-5-meth
ylpyrimidine,
2-(4'-fluorophenyl)-4-(1"-methyl-3"-trifluoromethylpyrazol-5"-yloxy)-6-meth
ylpyrimidine,
4-(2"-chloropyrid-4"-yloxy)-2-(2',4'-difluorophenyl)-5-methylpyrimidine,
4-(2"-chloropyrid-4"-yloxy)-5,6-dimethyl-2-(4'-trifluoromethoxyphenyl)pyrim
idine,
4-(2"-chloropyrid-4"-yloxy)-5,6-dimethyl-2-(4'-trifluoromethylphenyl)pyrimi
dine,
4-(2
"-chloropyrid-4"-yloxy)-5-methyl-2-(4'-trifluoromethoxyphenyl)pyrimidine,
4-(2'-chloropyrid-4"-yloxy)-5-methyl-2-(4'-trifiuoromethylphenyl)pyrimidine
4-(2"-chloropyrid-4"-yloxy)-6-methyl-2-(4'-trifluoromethoxyphenyl)pyrimidin
e,
4-(2"-chloropyrid-4"-yloxy)-6-methyl-2-(4'-trifluoromethylphenyl)pyrimidine
4-methyl-6-(4"-trifluoromethoxyphenyl)-2-(1'-methyl-3'-trifluoromethylpyraz
ol-5'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethoxyphenyl)-2-(2'-chloropyrid-4'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethoxyphenyl)-2-(2'-chloropyrid-4'-yloxy)
pyridine,
4-methyl-6-(4"-trifluoromethylphenyl)-2-(1'-methyl-3'-trifluoromethylpyrazo
l-5'-yloxy)pyridine,
4-methyl-6-(4"-trifluoromethylphenyl)-2-(2'-chloropyrid-4'-yloxy)pyridine,
5,6-dimethyl-2-(4'-trifluoromethoxyphenyl)-2-(1"-methyl-3"-trifluoromethylp
yrazol-5"-yloxy)pyrimidine,
5,6-dimethyl-2-(4'-trifluoromethoxyphenyl)-4-(3"-trifluoromethylphenoxy)pyr
imidine,
5,6-dimethyl-2-(4'-trifluoromethylphenyl)-4-(3"-trifluoromethylphenoxy)pyri
midine,
5,6-dimethyl-4-(1"-methyl-3"-trifluoromethylpyrazol-5"-yloxy)-2-(4'-trifluo
romethylphenyl)-pyrimidine,
5-methyl-2-(3'-methylphenyl)-4-(1"-methyl-3"-trifluoromethylpyrazol-5"-ylox
y)pyrimidine,
5-methyl-2-(3'-methylphenyl)-4-(3"-trifluoromethylphenoxy)pyrimidine,
5-methyl-2-(4'-trifluoromethoxyphenyl)-2-(1"-methyl-3"-trifluoromethylpyraz
ol-5"-yloxy)pyrimidine,
5-methyl-2-(4'-trifluoromethoxyphenyl)-4-(3"-trifluoromethylphenoxy)pyrimid
ine,
5-methyl-2-(4'-trifluoromethylphenyl)-4-(1"-methyl-3"-trifluoromethylpyrazo
l-5"-yloxy)pyrimidine,
5-methyl-4-(3"-trifluoromethylphenoxy)-2-(4'-trifluoromethylphenoxy)pyrimid
ine,
6-(4"-fluorophenyl)-2-(1'-methyl-3'-trifluoromethylpyrazol-5'-yloxy)pyridin
e,
6-methyl-2-(4'-trifluoromethoxyphenyl)-2-(1"-methyl-3"-trifluoromethylpyraz
ol-5"-yloxy)pyrimidine,
6-methyl-2-(4'-trifluoromethoxyphenyl)-4-(3"-trifluoromethylphenoxy)pyrimid
ine,
6-methyl-4-(3"-trifluoromethylphenoxy)-2-(4'-trifluoromethylphenyl)pyrimidi
ne, and the like.
The present invention also provides a process for the preparation
of a compound of general formula I, which comprises the reaction of
a compound of general formula III ##STR3## with a compound of
general formula IV
wherein Z, A, R.sup.1, R.sup.2, m, n and X are as defined
hereinbefore; Hal represents a halogen atom; and M represents a
metal atom.
The halogen atom Hal may be any halogen atom, suitably a fluorine,
chlorine or bromine atom. The metal atom M may be any metal atom,
suitably an alkali metal atom such as sodium and potassium.
In practice, the reaction may be carried out in the absence or
presence of a solvent which promotes the reaction or at least does
not interfere with it. Preferred are polar, aprotic solvents,
suitably being N,N-dimethylformamide or dimethylsulfoxide or
sulfolane or an ether, such as tetrahydrofurane or dioxane, or
mixtures thereof. The reaction is carried out at a temperature
between ambient temperature and the reflux temperature of the
reaction mixture, preferably at elevated temperature, especially
reflux temperature.
Compounds of formula III in which Z is C--H and n is 0 may be
obtained by reacting a compound of general formula V ##STR4##
wherein R.sup.2 and m are as defined hereinbefore, with an
aldehyde, suitably formaldehyde, and a dialkylamine, suitably
dimethylamine, according to Org. Synthesis Col. Vol. III, 305f, in
a solvent, conveniently an alcohol, preferably ethanol, to give a
compound of general formula VI, ##STR5## which is subsequently
reacted according to DBP 21 47 288 (1971) with an ammonium salt,
suitably ammonium acetate, and a compound of general formula VII,
##STR6## wherein Y is an alkoxy group or an NH.sub.2 -group,
preferably an ethoxy group, in a solvent, suitably an alcohol,
preferably ethanol, to give a compound of general formula VIII,
##STR7## which is further converted by reacting VIII with
phosphoryl halogenides (Mucller, E., Chem. Ber. 42, 423 (1909);
Katritzky et al., J. Chem. Soc., Perkin Trans. Part 1, 1980,
2743-2754), preferably phosphoryl bromide or phosphoryl chloride at
elevated temperatures, ideally reflux temperature, to give a
compound of general formula III.
An alternative, and preferred process for the preparation of
compounds of general formula III in which Z is C--H , comprises
reacting a 2,6-dihalopyridine of general formula IX ##STR8##
wherein R.sup.1 and n are as defined hereinbefore, and each
Hal.sub.1 and Hal.sub.2 independently represents a halogen atom,
with an in situ prepared metalated benzene derivative of general
formula (X) in an approximately equimolar ratio, ##STR9## wherein
R.sup.2 and m are as defined hereinbefore, and M represents an
alkali metal atom.
The alkali metal may be any alkali metal, preferably lithium, and
the reaction may be carried out in an aprotic, polar solvent,
preferably ethers, to give a compound of general formula III,
essentially as disclosed in Cook and Wakefield, J. Chem. Soc.,
1969, 2376.
A process for the preparation of compounds of formula III, in which
Z represents a nitrogen atom, comprises the reaction of benzamidine
hydrochlorides of the general formula XI ##STR10## wherein R.sup.2
and m are as defined hereinbefore with a compound of formula XII,
##STR11## wherein each R.sup.1.sub.1 and R.sup.1.sub.2
independently are as defined hereinbefore; and the O-alkyl group is
suitably methoxy or ethoxy, to give a pyrimidinone of general
formula XIII. ##STR12##
Compounds of general formula XI are known or may be prepared
according to procedures described in the art, for example in
Tetrahedron, 33, 1675f (1979) and J. Org. Chem., 26, 412f.
(1960).
The reaction of compounds of formulae XI and XII may be carried out
according to Liebigs Ann. 1980, 1392f in an organic solvent,
suitably an alcohol and preferably ethanol, and in the presence of
a base, suitably metal alkoxides, preferably sodium ethoxide.
Compounds of formula XIII may subsequently be converted into
compounds of formula III, essentially as described in Davies and
Pigott, J. Chem. Soc., 1945, 347, by reaction with a phosphoryl
halogenide or thionyl halogenide, preferably phosphoryl chloride,
ideally in the absence of a solvent, at elevated temperatures to
obtain compounds of formula III.
Compounds of general formula IV are known or may be prepared by
known methods. They may be prepared and isolated separately or may
be prepared in situ. Generally, a compound of general formula
XIV
wherein A and X are as hereinbefore defined is reacted with a
suitable metal base, for example a metal carbonate or hydride.
Preferably the metal salt is a sodium or potassium salt.
Compounds of general formula I may, if desired, be isolated and
purified using conventional techniques.
The present invention also provides the use of a compound of
general formula I as a herbicide. Further, in accordance with the
invention there is provided a method of combating undesired plant
growth at a locus by treating the locus with a composition
according to the invention or a compound of formula I. The
treatment may be a foliar spray application, the locus is most
suitably the plants in a crop area, typical crops being cereals,
maize, soya bean, sunflower or cotton. However, application may
also be to the soil for those compounds having pre-emergence
herbicidal action. The dosage of active ingredient used may, for
example be in the range of from 0.01 to 10 kg/ha, preferably 0.1 to
1 kg/ha.
The present invention also provides a herbicidal composition which
comprises a compound of formula I and at least one carrier.
Preferably there are at least two carriers in a composition of the
present invention, at least one of which is a surface-active
agent.
A carrier in a composition according to the invention is any
material with which the active ingredient is formulated to
facilitate application to the locus to be treated, which may be, as
appropriate, a plant, seed or soil, or to facilitate storage,
transport or handling. A carrier may be a solid or a liquid,
including a material which is normally gaseous but which has been
compressed to form a liquid, and any of the carriers normally used
in formulating herbicidal compositions may be used. Preferably
compositions according to the invention contain 0.5 to 95% by
weight of active ingredient.
Suitable solid carriers include natural and synthetic clays and
silicates, for example natural silicates such as diatomaceous
earths; magnesium silicates, for example talcs; magnesium aluminium
silicates, for example attapulgites and vermiculites; aluminium
silicates, for example kaolinites, montmorillonites and micas;
calcium carbonate; calcium sulphate; ammonium sulphate; synthetic
hydrated silicon oxides and synthetic calcium or aluminium
silicates; elements, for example carbon and sulphur; natural and
synthetic resins, for example coumaron resins, polyvinyl chloride,
and styrene polymers and copolymers; solid polychlorophenols;
bitumen; waxes; solid fertilisers, for example superphosphates.
Suitable liquid carriers include water; alcohols, for example
isopropanol and glycols; ketones, for example acetone, methyl ethyl
ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic
or araliphatic hydrocarbons, for example benzene, toluene and
xylene; petroleum fractions, for example kerosene and light mineral
oils; chlorinated hydrocarbons, for example carbon tetrachloride,
perchloroethylene and trichloroethane. Mixtures of different
liquids are often suitable.
Agricultural compositions are often formulated and transported in a
concentrated form which is subsequently diluted by the user before
application. The presence of small amounts of a carrier which is a
surface-active agent facilitates this process of dilution. Thus
preferably at least one carrier in a composition according to the
invention is a surface active agent. For example, the composition
may contain at least two carriers, at least one of which is a
surface-active agent.
A surface-active agent may be an emulsifying agent, a dispersing
agent or a wetting agent; it may be non-ionic or ionic. examples of
suitable surface-active agents include the sodium or calcium salts
of polyacrylic acids and lignin sulphonic acids; the condensation
products of fatty acids or aliphatic amines or amides containing at
least 12 carbon atoms in the molecule with ethylene oxide and/or
propylene oxide; fatty acid esters of glycerol, sorbitol, sucrose
or pentaerythrol; condensates of these with
ethylene oxide and/or propylene oxide; condensation products of
fatty alcohol or alkyl phenols, for example p-octylphenol or
p-octylcresol, with ethylene oxide and/or propylene oxide;
sulphates or sulphonates of these condensation products; alkali or
earth alkali metal salts, preferably sodium salts, or sulphuric or
sulphonic acd esters containing at least 10 carbon atoms in the
molecule, for example sodium lauryl sulphate, sodium secondary
alkyl sulphates, sodium salts of sulphonated castor oil, and sodium
alkylaryl sulphonates such as dodecylbenzene sulphonate; and
polymers of ethylene oxide and copolymers of ethylene oxide and
propylene oxide.
The herbicidal composition of the invention may also contain other
active ingredients, for example, compounds possessing insecticidal
or fungicidal properties, or other herbicides.
The following examples illustrate the invention. The structures of
the compounds prepared in the following examples were additionally
confirmed by NMR and mass spectrometry.
EXAMPLES
Example 1
.beta.-Dimethylamino propiophenone hydrochloride
Acetophenone (29.1 ml, 0.25 mol), para-formaldehyde (12.0 g, 0.40
mol) and dimethyl amine hydrochloride (28.5 g, 0.35 mol) are
suspended in ethanol (50 ml). Concentrated hydrochloric acid (0.5
ml) is added and the mixture is heated to reflux for 4 h. Then
acetone (200 ml) is added and the resulting clear solution is
allowed to cool to ambient temperature. The precipitate is
collected by filtration and crystallized from ethanol yielding the
title compound (40.7 g, 76.0% of theoretical yield) as colorless
crystals with mp. 158.degree. C.
Examples 2-4
Additional examples of general formula VI are prepared as
exemplified by Example 1. Details are given in Table I
TABLE I ______________________________________ (VI) ##STR13## Ex.
mp yield No. R.sup.2 (.degree. C.) (%)
______________________________________ 2 3-trifluoromethyl 157 63 3
2,4-dichloro 136 51 4 2,4-dimethyl 134 72
______________________________________
Example 5
6-Phenyl-2-pyridone
Ethyl 2-chloroacetate (10.6 ml, 0.1 mol) is slowly added to hot
(105.degree. C.) pyridine (8.9 ml, 0.11 mol whereby the temperature
is maintained in the range of 100.degree. C. to 110.degree. C. The
resulting brown oil is dissolved in ethanol (60 ml),
.beta.-dimethylamino propiophenone hydrochloride (17.7 g, 0.1 mol;
prepared according to Example 1) and ammonium acetate (60 g) are
added and the mixture is boiled under reflux for 4 h. After
cooling, the mixture is filtered and the solvent is evaporated in
vacuo. The residue is crystallized from water, collected by
filtration and purified by re-crystallization from toluene. The
title compound is obtained as colorless crystals (4.7 g, 28% of
th.) with mp. 200.degree. C.
Example 6-8
Additional examples are analogously prepared to Example 5. Details
are given in Table II.
TABLE II ______________________________________ (VII) ##STR14## Ex.
mp yield No. R.sup.2 (.degree. C.) (%)
______________________________________ 6 3-trifluoromethyl 174 36 7
2,4-dichloro 255 56 8 2,4-dimethyl 209 23
______________________________________
Example 9
2-Bromo-6-phenyl pyridine
A mixture of 6-phenyl pyridone (3 g, 17.5 mmol; prepared according
to Example 6) and phosphoryl bromide (7.2 g, 25.0 mmol) is heated
to 100.degree. C. for 5 h. The cooled mixture is poured into water
(40 ml) and the pH is adjusted to 9 by addition of saturated
aqueous sodium carbonate. Then the layers are separated and the
aqueous layer is extracted with ethyl acetate (50 ml). The combined
organic layers are dried with anhydrous magnesium sulphate and the
solvent is evaporated in vacuo. The crude product is crystallized
from aqueous ethanol. Subsequent purification by flash
chromatography (silica gel, hexane/ethyl acetate 9/1 v/v) gives
2-bromo-6-phenyl pyridine (3.1 g, 76% of th.) as light brown
crystals with mp 50.degree. C.
Examples 10-12
Additional compounds of general formula III are prepared by
procedures analogous to that of Example 9. Details are given in
Table III.
TABLE III ______________________________________ (III) ##STR15##
Ex. mp yield No. R.sup.2 (.degree. C.) (%)
______________________________________ 10 3-trifluoromethyl oil 82
11 2,4-dichloro 123 88 12 2,4-dimethyl oil 68
______________________________________
Example 13
2-(1'-Methyl-3'-trifluromethyl pyrazol-5'-yloxy) 6-phenyl
pyridine
A mixture of 2-bromo-6-phenyl pyridine (0.5 g, 2.1 mmol; prepared
according to Example 9), 1-methyl-3-fluoromethyl-5-hydroxypyrazole
(0.65 9, 3.9 mmol), potassium carbonate (0.6 g, 4.3 mmol) and
N,N-dimethyl formamide (2 ml) are heated to reflux for 12 h. Then
the reaction mixture is directly applied onto a flash
chromatography column (silica gel). Elution with hexanelethyl
acetate (9/1 v/v) gives the title compound (0.35 g, 52.0% of th.)
as light-yellow oil.
Examples 14-16
The compounds specified in Table 4 are obtained by procedures
analogous to that of Example 13.
TABLE IV ______________________________________ (I) ##STR16## Ex.
mp yield No. A R.sup.2 (.degree. C.) (%)
______________________________________ 14 1'-CH.sub.3 -3'-CF.sub.3
-pyrazol-5'- 3"-CF.sub.3 113 93 yl 15 1'-CH.sub.3 -3'-CF.sub.3
-pyrazol-5'- 2",4"-dichloro 91 78 yl 16 1'-CH.sub.3 -3'-CF.sub.3
-pyrazol-5'- 2",4"- oil 95 yl dimethyl
______________________________________
Example 17
2-Fluoro-6-(4'-fluorophenyl)-pyridine
Butyl lithium (105.0 ml, 0.26 mol, 2.5 M solution in hexane) is
added to a solution of 1-bromo-4-fluoro benzene (34. 3 ml, 0.31
mol) in anhydrous diethyl ether (200 ml) at -20.degree. C. The
mixture is stirred for 60 min and then chilled to -40.degree. C.
2,6-Difluoropyridine (22.7 ml, 0.25 mol) is added and the reaction
mixture is allowed to warm to ambient temperature. Subsequently,
the mixture is washed with saturated aqueous ammonium chloride (300
ml). The layers are separated and the aqueous layer is washed with
diethyl ether 3 times (100 ml each). After drying of the combined
organic layers with anhydrous magnesium sulphate, the solvent is
removed in vacuo. The crude product is purified by flash column
chromatography (silica gel, hexane/AcOEt 8/2) yielding colorless
crystals of 2-fluoro-6-(4'-fluorophenyl)-pyridine (19.8 g, 41.0% of
th.) with mp 34.degree. C.
Examples 18-19
Analogously to Example 17, the examples of general formula III are
prepared as specified in Table V.
TABLE V ______________________________________ (III) ##STR17## Ex.
mp yield No. R.sup.1 R.sup.2 (.degree. C.) (%)
______________________________________ 18 -- -- oil 47 19 -- 4'- 58
75 trifluoromethyl 20 -- 3'- oil 72 trifluoromethyl
______________________________________
Example 21
2-(3'-Chlorpyrid-5'-yloxy)-6-(4"-fluorophenvloxy)-pyridine
A mixture of 2-fluoro-6-(4'-fluorophenyl)-pyridine (1.9 g, 10.0
mmol, prepared according to Example 17), 3-chloro-5-hydroxpyridine
(1.4 g, 11.0 mmol) and potassium carbonate (1.5 g, 11.0 mmol) in
sulfolane (10 ml) is heated to reflux for 8 h. The mixture is
allowed to cool to ambient temperature and is then filtered through
a bed of silica gel which is subsequently washed with ethyl
acetate. The organic solutions are combined and the solvent is
evaporated in vacuo. The remaining material is applied onto the top
of a flash chromatography column (silica gel) and eluted with
hexane/ethyl acetate. Elution with hexanelethyl acetate (8/2 v/v)
gives 2-(3'-chlorpyrid-5'-yloxy)-6-(4"-fluorophenyloxy)-pyridine
(1.4 g, 46% of th.) as light brown crystals with mp 139.degree.
C.
Examples 22-30
Additional compounds are prepared analogously to Example 21.
Details are found in Table VI.
TABLE VI ______________________________________ (I) ##STR18## Ex.
mp yield No. R.sup.1 A R.sup.2 (.degree. C.) (%)
______________________________________ 22 -- 3'-CF.sub.3 -phenyl
4"-fluoro oil 48 23 -- 2'-chloropyrid-4'-yl 4"-fluoro 137 37 24 --
2'-chloropyrid-4'-yl 109 35 25 -- 2'-chloropyrid-4'-yl 4"- 105 51
trifluoromethyl 26 -- 1'-CH.sub.3 -3'-CF.sub.3 -pyrazol-5'-
4"-fluoro 87 44 yl 27 -- 1'-CH.sub.3 -3'-CF.sub.3 -pyrazol-5'- 4"-
94 59 yl trifluoromethyl 28 -- 1'-CH.sub.3 -3'-CF.sub.3
-pyrazol-5'- 3"- 112 44 yl trifluoromethyl 29 --
2'-chloropyrid-4'-yl 3"- 92 54 trifluoromethyl 30 --
2',4'-difluorophenyl 3"- oil 72 trifluoromethyl
______________________________________
Example 31
4-Fluorobenzmidine hydrochloride
4-Fluorobenzonitrile (10 g, 83 mmol) is dissolved in a mixture of
anhydrous ethanol (5 ml) and diethyl ether (70 ml). The reaction
mixture is cooled to ice-bath temperature and saturated with
gaseous hydrogen chloride for 90 minutes. The mixture is allowed to
warm to ambient temperature and stirred overnight.
The colourless precipitates are filtered off, washed with diethyl
ether and dissolved in anhydrous ethanol (20 ml). Diethyl ether
(100 ml) saturated with gaseous ammonia is added and the solution
is stirred for 3 hours.
The resulting suspension filtered and the solvent of the filtrate
is removed in vacuo. The residue is washed with diisopropyl ether.
After drying colourless crystals (5.15 g, 35.5%) of melting point
210.degree. C. are obtained.
Examples 32 to 37
By method analogous to that of example 31, further compounds of the
general formula XI are prepared. Details are given in table
VII.
TABLE VII ______________________________________ (XI) ##STR19## Ex.
mp yield No. R.sup.2 (.degree. C.) (%)
______________________________________ 32 4-trifluoromethyl 167
21.4 33 3-methyl 243 29.7 34 3-chloro 148 17.5 35 3,4-diftuoro 185
17.4 36 3-trifluoromethyl 181 17.6 37 3-fluoro 143 20.0
______________________________________
Example 38
2-(4'-Fluorophenyl)-5-methyhl-4-pyrimidinone
Sodium hydride (0.52 g, 13 mmol) is added to 20 ml of anhydrous
ethanol and stirred for 30 minutes at ambient temperature. To this,
4-fluorobenzamidine hydrochloride (1.47 g, 8.5 mmol) (from example
1) is added and the mixture is stirred for further 30 minutes.
Methyl 2-formylpropionate (1 g, 10.6 mmol) is added dropwise and
the reaction mixture is left for 4 days under stirring at ambient
temperature.
After cooling, the solvent is removed in vacuo and the residue is
dissolved in aqueous sodium hydroxide (10 ml, 1M). Then the mixture
is brought to pH 5 with 2 molar hydrochloric acid. The precipitate
is filtered off and washed with diisopropyl ether. After drying,
colourless crystals (0.44 g, 10.3%) of melting point
>250.degree. C. are obtained.
Examples 39 to 55
By the method exemplified in example 38, further compounds of the
general formula III are prepared. Details are given in table
VIII.
TABLE VIII ______________________________________ (III) ##STR20##
Ex. mp yield No. R.sup.1 R.sup.2 (.degree. C.) (%)
______________________________________ 39 6-methyl 4'-fluoro 267
56.8 40 5-methyl 4'- >250 58.7 trifluoromethyl 41 6-methyl 4'-
209 82.2 trifluoromethyl 42 5-methyl 3'-methyl 169 34.3 43 6-methyl
3'-methyl 185 41.6 44 5-methyl 3'-chloro 260 61.4 45 6-methyl
3'-chloro 218 51.0 46 5-methyl 3',4'-difluoro >250 59.4 47
6-methyl 3',4'-difluoro 225 51.3 48 5-methyl 3'-trifluoromethyl 204
39.8 49 6-methyl 3'- 109 26.6 trifluoromethyl 50 5,6-dimethyl 3'-
215 70.4 trifluoromethyl 51 5,6-dimethyl 4'- 242 63.5
trifluoromethyl ______________________________________ 52 5-methyl
4'-chloro >250 27.2 53 6-methyl 4'-chloro 227 6.8 54 5-methyl
3'-fluoro 238 56.0 55 6-methyl 3'-fluoro 194 48.4
______________________________________
Examples 56
2-(4'-Fluorophenyl)-4-chloro-5-methylpyrimidine
A mixture of 2-(4'-fluorophenyl)-5-methyl-4-pyrimidinone (0.79 g,
3.9 mmol) (from example 5) and phosphorus oxychloride (3 ml) is
heated to reflux for 1 hour.
The main excess of phosphorous oxychloride is removed in vacuo and
the residue is quenched with water (10 ml) to hydrolyze the
remaining reagent. The mixture is neutralized and then extracted
with ethyl acetate (50 ml). After drying of the organic layer with
anhydrous magnesium sulphate, the solvent is removed in vacuo. The
title compound (0.63 g, 72.6%) is obtained as colourless crystals
of melting point 133.degree..
Examples 57-73
The compounds of general formula (XIII) listed in table IX are
prepared analogously to the method of example 56.
TABLE IX ______________________________________ (III) ##STR21## Ex.
mp yield No. R.sup.1 R.sup.2 (.degree. C.) (%)
______________________________________ 57 6-methyl 4'-fluoro 143
97.0 58 6-methyl 4'- 62 71.8 trifluoromethyl 59 5-methyl 4'- 109
87.3 trifluoromethyl 60 5-methyl 3'-methyl 154 98.8 61 6-methyl
3'-methyl 134 73.7 62 5-methyl 3'-chloro 87 94.1 63 6-methyl
3'-chloro 101 26.1 64 5-methyl 3',4'-difluoro 114 92.0 65 6-methyl
3',4'-difluoro 94 90.7 66 5,6-dimethyl 3'- 83 81.6 trifluoromethyl
67 5,6-dimethyl 4'- 57 54.5 trifluoromethyl 68 5-methyl 3'- 101
81.4 trifluoromethyl 69 6-methyl 3'- 62 87.3 trifluoromethyl 70
5-methyl 4'-chloro 162 85.2 71 6-methyl 4'-chloro 101 83.6 72
5-methyl 3'-fluoro 95 83.7 73 6-methyl 3'-fluoro 86 71.5
______________________________________
Example 74
2-(4'-Fluorophenyl)-4-(3"-trifluoromethylphenoxy)-6-methylpyrimidine
A mixture of 2-(4'-fluorophenyl)-4-chloro-6-methylpyridine (0.6 g,
2.7 mmol) (from example 14), a,a,a,-3-hydroxybenzotrifluoride (0.49
g, 3 mmol) and potassium carbonate (0.41 g, 3 mmol) in
N,N-dimethylformamide (3 ml) is heated to reflux for 2 hours.
After cooling, ethyl acetate (10 ml) is added and the suspension is
filtered through a bed of silica gel using ethyl acetate. The
solvent of the filtrate is removed in vacuo and the residue
purified by flash silica gel column chromatography using
hexane/ethyl acetate 7/2.
Removal of the solvent affords colourless crystals (0.53 g, 56.4%)
of melting point 58.degree. C.
Examples 75-97
Further compounds of the general formula I are prepared by the
procedure of example 74. Details are given in table X.
TABLE X ______________________________________ (I) ##STR22## Ex. mp
yield No. R.sup.1 R.sup.2 A (.degree. C.) (%)
______________________________________ 75 5-methyl 4'-fluoro
1"-CH.sub.3 -3"-CF.sub.3 -pyrazo(-5"- 133 54.7 yloxy 76 6-methyl
4'-fluoro 3"-CF.sub.3 -phenoxy 123 21.0 77 6-methyl 4'-CF.sub.3
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 98 39.5 yloxy 78 6-methyl
4'-CF.sub.3 3"-CF.sub.3 -phenoxy 89 79.9 79 5-methyl 4'-CF.sub.3
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 147 27.6 yloxy 80 5-methyl
4'-CF.sub.3 3"-CF.sub.3 -phenoxy 95 97.6 81 5-methyl 3'-CH.sub.3
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 121 74.9 yloxy 82 5-methyl
3'-CH.sub.3 3"-CF.sub.3 -phenoxy 71 74.5 83 6-methyl 3'-CH.sub.3
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 113 74.9 yloxy 84 6-methyl
3'-CH.sub.3 3"-CF.sub.3 -phenoxy 60 73.2 85 5-methyl 3'-chloro
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 116 35.4 yloxy 86 5-methyl
3'-chloro 3"-CF.sub.3 -phenoxy 105 52.4 87 6-methyl 3'-chloro
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 96 27.1 yloxy 88 5-methyl
2',4'- 3"-CF.sub.3 -phenoxy 68 40.4 difluoro 89 5-methyl 2',4'-
2"-chloropyrid-4"-yloxy 146 58.8 difluoro 90 6-methyl 2',4'-
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 78 56.4 difluoro yloxy 91
6-methyl 2',4'- 3"-CF.sub.3 -phenoxy 64 65.3 difluoro 92 6-methyl
2',4'- 2"-chloropyrid-4"-yloxy 162 31.7 difluoro 93 5-methyl
4'-CF.sub.3 2"-chloropyrid-4"-yloxy 99 44.1 94 5,6- 4'-CF.sub.3
1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 136 13.2 dimethyl yloxy 95
5,6- 4'-CF.sub.3 3"-CF.sub.3 -phenoxy 73 65.6 dimethyl 96 5,6-
3'-CF.sub.3 1"-CH.sub.3 -3"-CF.sub.3 -pyrazol-5"- 132 30.3 dimethyl
yloxy 97 5,6- 3'-CF.sub.3 3"-CF.sub.3 -phenoxy 105 67.5 dimethyl
______________________________________
Example 98
Herbicidal Activity
To evaluate their herbicidal activity, compounds according to the
invention are tested using a representative range of plants:
______________________________________ TRZAS Triticum aestivum
HORVW Hordeum vulgare GOSHI Gossypium hirsutum HELAN Helianthus
annuus ORYSA Oryza sativa GLXMA Glycine max BEAVA Beta vulgaris
ZEAMX Zea mays ALOMY Alopecurus myosuroides AVEFA Avena fatua ECHCG
Echinocloa crus-galli SETVI Setaria viridis GALAP Galium aparine
STEME Stellaria media CHEAL Chenopodium album VERPE Veronica
persica LAMPU Lamium purpureum VIOAR Viola arvensis SIDSP Sida
spinosa AMBAR Ambrosia artemisifolia ABUTH Abutilon theophrasti
IPOPU Ipomoea purpurea SINAL Sinapis alba AMARE Amaranthus
retroflexus ______________________________________
The tests fall into two categories, pre-emergence and
post-emergence. The pre-emergence tests involve spraying a liquid
formulation of the compound onto the soil in which the seeds of the
plant species mentioned above had recently be sown. The
post-emergence tests involve spraying seedlings of the above
species with a such a formulation.
The soil used in the tests is a prepared horticultural loam. The
formulations used in the test are prepared from solutions of the
test compounds in acetone containing 0.4% by weight of an
alkylphenyl/ethylene oxide condensate surfactant available under
the trade mark TRITON.times.155. The acetone solutions are diluted
with water and the resulting formulations at dosage levels
corresponding to 1000 g or 300 g of active material per hectare in
a volume equivalent to 400 litres per hectare. In the pre-emergence
tests untreated sown soil and in the
post-emergence tests untreated soil bearing untreated seedling
plants are used as controls.
The herbicidal effects of the test compounds are assessed visually
twenty days after spraying the foliage and the soil (in the case of
examples 13-16 thirteen days after treatment) and are recorded on a
0-9 scale. A rating 0 indicates growth as untreated control, a
rating 9 indicates death. An increase of 1 unit on the linear scale
approximates to a 10% increase in the level of effect. An asterisk
indicates that the specified plant species was not treated in the
test.
The results of the test are set out in the table shown below in
which the compounds are identified by reference to the preceding
examples. An asterisk indicates that the specified plant species
was not treated in the test.
__________________________________________________________________________
Ex. dose appl. GLXM ZEAM ALOM No g/ha time TRZAW HORVW GOSHI HELAN
ORYSA A BEAVA X Y AVEFA ECHCG
__________________________________________________________________________
13 1000 pre * * * * 0 0 4 2 * 2 4 post * * * * 2 5 8 4 * 2 5 14
1000 pre * * * * 3 4 9 9 * 6 8 post * * * * 4 6 9 6 * 6 7 15 1000
pre * * * * 0 2 8 2 * 2 5 post * * * * 2 6 9 5 * 2 7 16 1000 pre *
* * * 0 0 2 0 * 0 2 post * * * * 0 2 7 4 * 2 2 21 300 pre 1 0 0 0 *
* * 0 0 * * post 0 0 1 1 * * * 1 0 * * 22 300 pre 0 0 0 0 * * * 0 0
* * post 0 0 1 2 * * * 2 0 * * 23 300 pre 1 0 * 1 * * * 1 * * *
post 1 2 * 3 * * * 2 * * * 24 300 pre 0 0 * 0 * * * 0 * * * post 2
2 * 3 * * * 3 * * * 25 300 pre 0 3 0 0 * * * 3 5 * 6 post 3 3 4 5 *
* * 4 5 * 4 26 300 pre 0 1 * 0 * * * 0 * * * post 4 3 * 4 * * * 3 *
* * 27 300 pre 4 6 3 3 * * * 4 9 * 8 post 4 5 6 6 * * * 4 6 * 6 28
300 pre 1 4 2 0 * 3 * 1 8 * 5 post 3 5 8 5 * 5 * 8 7 * 4 29 300 pre
1 0 0 0 * 0 * 0 3 * 2 post 2 2 5 4 * 3 * 3 3 * 2 30 300 pre 2 0 0 0
* 2 * 0 0 * 0 post 0 0 0 0 * 0 * 0 0 * 0 74 300 pre 0 0 0 0 * * * 0
0 * 0 post 0 0 2 0 * * * 0 0 * 0 75 300 pre 3 4 2 1 * * * 2 8 * 6
post 4 5 6 6 * * * 4 7 * 7 76 300 pre 1 3 0 0 * * * 0 8 * * post 3
3 5 5 * * * 4 4 * * 77 300 pre 3 5 6 3 * 5 * 4 9 * 8 post 4 5 8 8 *
8 * 5 7 * 6 78 300 pre 3 6 6 2 * 3 * 3 9 * 8 post 4 5 8 8 * 8 * 5 6
* 7 79 300 pre 4 5 8 3 * 4 * 3 8 * 8 post 4 5 8 6 * 6 * 6 8 * 5 80
300 pre 4 7 8 3 * 5 * 4 8 * 8 post 4 6 9 8 * 8 * 6 7 * 6 81 300 pre
0 3 0 0 0 * 0 * 6 * 4 post 2 3 4 4 * 5 * 3 3 * 2 82 300 pre 0 2 0 0
* 0 * 2 7 * 5 post 3 3 4 4 * 4 * 4 4 * 3 83 300 pre 0 0 0 0 * 0 * 0
3 * 4 post 0 2 4 4 * 3 * 2 3 * 3 84 300 pre 0 0 0 0 * 0 * 0 0 * 1
post 0 2 0 2 * 1 * 1 1 * 0 85 300 pre 1 3 2 0 * 0 * 2 8 * 6 post 2
4 5 4 * 5 * 3 5 * 4 86 300 pre 2 3 2 0 * 1 * 3 8 * 7 post 3 4 8 4 *
5 * 5 5 * 6 87 300 pre * * * * * * * * * * * post * * * * * * * * *
* * 88 300 pre 0 0 0 0 * 0 * 0 0 * 0 post 1 1 2 3 * 2 * 1 1 * 2 89
300 pre 1 3 2 1 * 5 * 5 5 * 6 post 4 4 6 5 * 5 * 5 5 * 6 90 300 pre
3 4 3 2 * 3 * 5 8 * 7 post 4 5 5 5 * 6 * 5 5 * 6 91 300 pre 0 0 0 0
* 0 * 0 3 * 0 post 2 2 5 4 * 3 * 3 3 * 3 92 300 pre 0 0 1 0 * 0 * 2
2 * 0 post 0 1 4 3 * 2 * 2 3 * 2 93 300 pre 4 5 7 2 * 3 * 5 8 * 7
post 5 5 6 5 * 5 * 6 6 * 7 94 300 pre 3 3 5 4 * 3 * 3 8 * 6 post 2
4 7 5 * 5 * 3 5 * 5 95 300 pre 2 5 3 2 * 3 * 3 7 * 6 post 2 4 6 5 *
5 * 4 5 * 5 96 300 pre 0 0 2 2 * 0 * 2 1 * 0 post 1 1 3 4 * 2 * 1 2
* 2 97 300 pre 0 0 0 0 * 3 * 0 0 * 0 post 0 1 3 2 * 2 * 1 0 * 1
__________________________________________________________________________
STEM LAM AM AM SETVI GALAP E CHEAL VERPE PU VIOAR SIDSP BAR ABUTH
IPOPU SINAL ARE
__________________________________________________________________________
13 * * * * * * * * * * * 5 * * * * * * * * * * * * 8 * 14 * * * * *
* * * * * * 8 * * * * * * * * * * * * 8 * 15 * * * * * * * * * * *
6 * * * * * * * * * * * * 6 * 16 * * * * * * * * * * * 2 * * * * *
* * * * * * * 5 * 21 0 0 0 * 0 * 0 * * * 0 * * 0 0 0 * 0 * 0 * * *
0 * * 22 1 0 0 * 0 * 0 * * * 0 * * 0 0 0 * 1 * 1 * * * 1 * * 23 0 2
0 0 0 * * * * 0 0 * 0 0 2 4 0 4 * * * * 4 1 * 5 24 0 0 0 0 0 * * *
* 0 0 * 0 1 1 2 0 3 * * * * 3 2 * 4 25 9 2 7 * 9 8 8 4 4 4 2 * 9 6
5 4 * 6 * 6 6 5 4 4 * 6 26 8 0 7 8 8 * * * * 0 0 * 9 3 3 5 6 8 * *
* * 5 4 * 7 27 9 6 9 * 9 9 8 8 8 6 6 * 9 7 5 6 * 6 * 7 8 5 6 6 * 5
28 9 7 9 * 9 9 8 * * 8 5 * 9 7 6 7 * 9 7 8 * * 8 6 * 7 29 8 1 6 * 8
3 8 * * 3 1 * 9 4 4 5 * 9 5 7 * * 4 5 * 5 30 0 0 0 * 0 0 0 * * 0 5
* 0 2 0 0 * 0 0 0 * * 0 1 * 0 74 0 0 0 6 0 0 0 0 * 0 0 * 6 1 0 0 0
7 0 0 1 * 0 2 * 1 75 9 2 9 * 9 9 9 9 * 5 3 * 9 6 8 7 * 9 7 8 6 * 6
4 * 6 76 9 5 9 8 9 8 * 6 * 5 3 * 9 6 6 8 9 9 8 * 6 * 6 4 * 6 77 9 8
9 * 9 9 8 * * 8 9 * 9 8 7 8 * 9 8 9 * * 8 7 * 8 78 9 8 9 * 9 8 8 *
* 9 9 * 9 9 7 8 * 9 8 8 * * 8 8 * 7 79 9 8 9 * 9 8 8 * * 9 9 * 9 8
7 8 * 9 8 8 * * 8 8 * 7 80 9 8 9 * 9 9 8 * * 9 9 * 9 8 7 8 * 8 8 8
* * 8 8 * 8 81 9 0 6 * 9 8 7 * * 2 4 * 8 8 3 4 * 9 7 5 * * 4 5 * 5
82 9 1 5 * 9 6 8 * * 4 4 * 9 4 4 4 * 9 5 7 * * 4 5 * 7 83 7 1 2 * 8
3 7 * * 1 2 * 9 4 3 3 * 9 4 5 * * 2 4 * 5 84 0 0 0 * 0 0 2 * * 0 0
* 0 1 2 2 * 3 1 5 * * 1 3 * 4 85 9 6 9 * 8 8 8 * * 5 5 * 9 5 6 4 *
9 8 7 * * 5 4 * 5 86 9 3 8 * 9 7 8 * 5 4 * 9 7 6 5 * 9 7 8 * * 4 5
* 6
87 * * * * * * * * * * * * * * * * * * * * * * * * * * 88 0 0 0 * 2
2 4 * * 0 0 * 4 2 3 4 * 5 3 5 * * 2 6 * 4 89 8 3 9 * 9 8 9 * * 7 9
* 9 7 4 5 * 9 6 8 * * 6 7 * 6 90 9 4 9 * 9 9 9 * * 9 7 * 9 7 5 6 *
9 6 8 * * 5 7 * 6 91 9 1 7 * 8 4 8 * * 2 3 * 9 3 4 4 * 9 5 8 * * 4
6 * 5 92 8 0 7 * 7 3 8 * * 2 4 * 8 4 3 5 * 6 4 8 * * 4 6 * 6 93 9 5
9 * 9 9 9 * * 9 9 * 9 7 6 6 * 9 6 8 * * 6 8 * 7 94 9 5 9 * 9 9 9 *
* 9 9 * 9 6 5 5 * 9 6 8 * * 6 9 * 6 95 9 4 9 * 9 6 9 * * 7 6 * 8 7
5 6 * 8 6 8 * * 5 9 * 6 96 8 0 4 * 7 0 8 * * 0 5 * 8 2 4 4 * 7 4 7
* * 4 5 * 4 97 3 0 0 * 0 0 3 * * 0 3 * 5 2 3 3 * 4 3 5 * * 2 5 * 5
__________________________________________________________________________
* * * * *